Urinary nuclear magnetic resonance spectroscopy of a Bangladeshi cohort with hepatitis-B hepatocellular carcinoma: A biomarker corroboration study

Table 1 Subject demographics of the Bangladeshi study cohort

Group	n	Age (yr), median (range)	M:F (%male)	Etiology, n	HBeAg positive	Height (cm), median (range)	Weight (kg), median (range)	BMI (kg/m2), median (range)
CTR	7	37 (24-46)	7:0 (100%)	NA	NA	170 (152-173)	65 (54-85)	26.0 (18.7-29.4)
CHB	46	27 (15-45)	40:6 (87%)	HBV (100%)	27	166 (147- 180)	55 (35-79)	20.6 (13.9-26.6)
					(-59%)
CIR	47	42 (15-67)	39:8 (83%)	HBV (98%)	21	165 (142–175)	58 (42-82)	21.9 (14.9-29.3)
				Cryptogenic HBV (2%)	(-45%)
HCC	42	48 (27-90)	38:3 (90%)	HBV (93%)	15	162 (145-180)	48 (38-75)	18.3 (12.3-25.2)
				HCV (2%)	(-36%)
				Cryptogenic (5%)

CTR: Healthy controls; CHB: Chronic hepatitis-B related liver disease; CIR: Cirrhosis; HCC: Hepatocellular carcinoma; NA: Unavailable; BMI: Body mass index.

Table 2 Serum biochemistry profiles

Group	ALT	ALP	Bil	Alb	AFP	Creatinine
	(U/L)	(U/L)	(mg/dL)	(g/dL)	(ng/mL)	(mg/dL)
CTR	31 (18-42) [7/7]	NA	NA	NA	NA	NA
CHB	40 (22-232) [32/46]	96 (63-171) [14/46]	1.4 (0.4-2.2) [5/46]	3.4 (2.9-3.9) [2/46]	NA	1.4 (1.3-1.5) [2/46]
CIR	51 (10-243) [30/47]	286 (75-558) [5/47]	1.9 (0.3-22.4) [19/47]	2.7 (1.5-39.0) [20/47]	6 (2-12) [4/47]	1.4 (0.8-2.8) [17/47]
HCC	74 (28-332) [32/42]	259 (82-648) [25/42]	1.8 (0.3-21.5) [28/42]	3.1 (1.3-35.0) [26/42]	4900 (4-70000) [34/42]	0.9 (0.4-1.3) [23/42]

Data are represented as median (range) [number of subjects included/total number of subjects in subgroup]. CTR: Healthy controls; CHB: Chronic hepatitis-B related liver disease; CIR: Cirrhosis; HCC: Hepatocellular carcinoma; ALT: Alanine transaminase; ALP: Alkaline phosphatase; Bil: Bilirubin; Alb: Albumin; AFP: α-fetoprotein; NA: Unavailable.

Table 3 Comparison of relative signal levels (mean ± SD) of discriminatory metabolites between study cohorts¹

Selected metabolites		Study cohort (number of subjects in group)				P value2
Metabolite	δ/ppm (multiplicity) of peak analysed	CTR (n = 7)	CHB (n = 46)	CIR (n = 47)	HCC (n = 42)
Acetate	1.92 (s)	0.34 ± 0.03	0.57 ± 0.64	1.70 ± 2.14	1.24 ± 1.49	0.007
Carnitine	3.23 (s)	0.57 ± 0.41	0.42 ± 0.22	0.44 ± 0.53	1.19 ± 1.04	0.000
Citrate	2.52 (d)	1.49 ± 0.61	1.35 ± 0.61	1.19 ± 1.21	1.07 ± 0.46	0.005
Creatine	3.03 (s)	1.34 ± 0.35	1.24 ± 0.38	1.07 ± 0.95	1.54 ± 1.82	0.007
Creatinine	3.04 (s)	10.88 ± 1.30	10.06 ± 1.76	7.74 ± 3.00	5.85 ± 1.83	0.000
DMA	2.72 (s)	2.14 ± 0.57	2.11 ± 0.58	1.95 ± 1.21	1.91 ± 0.45	0.022
Formate	8.46 (s)	0.07 ± 0.03	0.07 ± 0.05	0.16 ± 0.16	0.16 ± 0.18	0.059
Glycine	3.56 (s)	1.04 ± 0.39	0.84 ± 0.42	0.74 ± 0.38	0.79 ± 0.63	0.129
Hippurate	7.85 (d)	0.99 ± 0.47	0.85 ± 0.47	0.44 ± 0.35	0.28 ± 0.30	0.000
TMAO	3.27 (s)	1.79 ± 0.44	1.95 ± 0.77	1.62 ± 1.04	1.32 ± 0.75	0.000

¹Percentage normalised metabolite signal level relative to total NMR signal in the region 0.50-9.50 ppm (excluding 4.50-6.40 ppm);

²Significance for independent samples Kruskal-Wallis one-way ANOVA test with pairwise multiple comparisons. CTR: Healthy controls; CHB: Chronic hepatitis-B related liver disease; CIR: Cirrhosis; HCC: Hepatocellular carcinoma.